59 results about "Matrix metalloproteinase" patented technology

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.

The invention belongs to the field of biological medicines, and finds and verifies that taquinimod or pharmaceutically acceptable salts thereof can be used for preparing medicines for treating endometriosis for the first time, and is particularly suitable for progestogen-resistant, recurrent or deep infiltration type endometriosis. The action mechanism of the taquinimod is as follows: the taquinimod can down-regulate the expression of S100A9 protein and reduce the infiltration of S100A9 + macrophages by inhibiting an NF-kappa B signal channel so as to further inhibit the expression of a vascular endothelial growth factor receptor 1 (VEGFR1) and a matrix metalloproteinase 2 (MMP2), finally block pathological angiogenesis and inhibit the growth of ectopic lesions. Animal experiments show that the taquinimod can significantly reduce the number and weight of nidus of a mouse model with endometriosis. The invention provides a brand-new non-hormone treatment choice with a clear action mechanism for clinical application, provides a pharmaceutical composition containing a specific dosage and a drug combination scheme, and has an important clinical value.

The invention discloses iron oxide nanoparticles capable of responding to particle size change in a tumor microenvironment and a preparation method of the iron oxide nanoparticles, and belongs to the technical field of biomedical nano materials. The nano-particle comprises an iron oxide nano-crystal core with the particle size of 3-5nm and a tumor microenvironment response layer coating the surface of the iron oxide nano-crystal core. The response layer contains groups, such as disulfide bonds, enzyme digestion peptide fragments and the like, which can respond to acidic pH, high-concentration reduced glutathione or matrix metalloproteinase and other tumor characteristic stimuli to generate structural changes. In a tumor microenvironment, the hydration particle size of the nanoparticles can be directionally and controllably converted from 3-20 nm to 20-100 nm (or reversely). The preparation method mainly comprises two steps of preparing the core by a thermal decomposition method and modifying the surface response layer. The technical problems of insufficient tumor targeted enrichment capacity, limited imaging contrast and difficulty in balancing permeation and retention caused by fixed particle size of the existing iron oxide nanoparticles are solved, and the accuracy and efficiency of tumor diagnosis and treatment can be remarkably improved.

The invention discloses a functional lipid compound for nano-liposome wrapping and a preparation method, and relates to the technical field of functional lipid compounds, the functional lipid compound comprises (a) a polyphenol-lipid covalent conjugate which is composed of a polyphenol active unit selected from curcumin, dihydroquercetin or derivatives thereof, and (b) a lipid covalent conjugate which is composed of a polyphenols active unit selected from curcumin, dihydroquercetin or derivatives thereof and a polyphenols active unit selected from curcumin, dihydroquercetin or derivatives thereof; the conjugate is covalently linked to a phosphatidyl ethanolamine or cholesterol skeleton through a cleavable linking group, and the conjugate can be integrated into a nano-liposome membrane and has the functions of structural support and biological activity; (b) a microenvironment-responsive functional phospholipid, which is a phospholipid derivative having a functional group responsive to an inflammatory microenvironment specific stimulus modified on a hydrophilic head group or a hydrophobic chain of a phospholipid molecule, the specific stimulus being selected from local pH < = 6.5, reactive oxygen species (ROS) concentration > = 10 [mu] M or matrix metalloproteinase MMP-2 / 9 overexpression; and (c) a bionic exosome membrane lipid component, wherein the bionic exosome membrane lipid component comprises sphingosine-based glycolipid or sulfated cholesterol separated from the plant-derived exosome.

The present invention relates to a novel Lactobacillus acidophilus strain. Also, the present invention relates to uses of the Lactobacillus acidophilus strain for antibacterial activity, antioxidation, the suppression of periodontal tissue damage or degradation, and anti-inflammation. Also, the present invention relates to a composition comprising the Lactobacillus acidophilus strain. The Lactobacillus acidophilus strain of the present invention can exhibit antibacterial activity against oral harmful bacteria that cause oral diseases, suppress the production of reactive oxygen species (ROS), inhibit the expression or activity of matrix metalloproteinase-3 (MMP-3) that causes periodontal tissue damage or degradation, and inhibit the expression or activity of inflammatory cytokines IL-6 and IL-8. Therefore, the strain and the composition comprising same, of the present invention, can be effectively used for antibacterial activity, antioxidation, the suppression of periodontal tissue damage or degradation, and anti-inflammation, and can also be used for treating, ameliorating or preventing oral diseases.

The invention relates to the technical field of electrochemical sensing, in particular to a multi-channel electrochemical aptamer sensor and a preparation method and application thereof.The multi-channel electrochemical aptamer sensor adopts a commercial silk-screen printing electrode and is combined with a polymer substrate material for amplifying electrochemical signals, and the electrochemical aptamer sensor is prepared. According to the present invention, the corresponding aptamer is fixed by using the gold nanoparticle through the chemical bond so as to specifically detect the three hemorrhage conversion biomarkers after acute cerebral infarction, such as human matrix metalloproteinase (MMP-9), fibrinogen (FN) and plasminogen activation inhibitor (PAI-1); wherein the FN and the PAI-1 are detected through an electrochemical aptamer sensor method for the first time, and simultaneous detection of the three biomarkers is realized through integration with commercial multi-channel micro electrochemical equipment.

This invention discloses an enzyme- and pH-responsive nucleic acid loading and delivery material and its preparation method. The material can be used for efficient loading and delivery of nucleic acid molecules. The preparation method uses amphiphilic zwitterionic monomers to improve the reverse emulsion polymerization system, enhancing polymerization at the two-phase interface and avoiding the extrusion effect of polymerization in the aqueous core on nucleic acid molecules, thereby improving the loading efficiency of nucleic acid molecules. Further preparation of cross-linking agents MP-CL and CB-CL, which can cleave in response to matrix metalloproteinase II or cathepsin B, endows the nanogel with the ability to respond to charge reversal in the tumor matrix and to release nucleic acid molecules from tumor cells. The acid-sensitive blocks on the amphiphilic monomers give the nanogel lysosomal escape capability. The delivery material can efficiently deliver nucleic acid molecules into cells and exhibits excellent stability and biosafety.

This invention relates to the field of biomedicine and discloses a composition for treating non-small cell lung cancer metastasis that targets replication stress vulnerability and its application. The composition includes a dual-responsive polymer prodrug, which consists of a block copolymer backbone, a matrix metalloproteinase cleavage peptide sequence coupled to the hydrophilic end, and an active molecular group coupled to the hydrophobic end based on an asymmetric grafting structure. The active molecular group comprises a replication stress inducer and an ATR kinase inhibitor. This invention maintains the amorphous phase of the micelle core through the asymmetric grafting structure, eliminating the permeation barrier caused by spontaneous crystallization of components. This amorphous core provides a proton permeation channel, ensuring the synchronous in-situ release of multiple target drugs, thereby blocking the DNA replication fork repair pathway and inducing mitotic catastrophe, maintaining the spatiotemporal overlap of multiple drug interventions in the pathological target area, and avoiding the risk of drug resistance.

This invention discloses a sodium alginate cross-linked matrix metalloproteinase-sensitive peptide-loaded dexamethasone sodium phosphate hydrogel and its preparation method. The dexamethasone-loaded hydrogel has good injectability. After injection, it is cleaved by MMPs at the site of inflammation in an inflammatory environment to release dexamethasone, exhibiting good sustained-release effect. It achieves targeted and long-acting treatment of inflammatory arthritis, osteoarthritis or other inflammatory diseases, and reduces the frequency of repeated intra-articular injections of glucocorticoids.

The application relates to the field of biological medicine, and discloses ascorbyl palmitate nanoliposomes capable of inducing tumor cell oncosis, a preparation method and application thereof. The nanoliposomes are constructed by inserting ascorbyl palmitate as a lipid component into a phospholipid bilayer, and are prepared by a film dispersion method from lecithin, cholesterol, pegylated phospholipid and ascorbyl palmitate. The average particle size of the nanoliposomes is 80-150 nm, the encapsulation rate is high, and the stability is good. The nanoliposomes can be administered through a tail vein, utilize the specific hydrolysis of matrix metalloproteinase MMP-2 which is highly expressed by tumor cells to hydrolyze ascorbyl palmitate, release palmitic acid and ascorbic acid, thereby inducing Caspase-independent oncosis of tumor cells, effectively overcoming apoptosis-related drug resistance, and reversing a tumor immunosuppressive microenvironment. The nanoliposomes avoid the cumulative toxicity of metal-type inducers, and provide a new safe and effective option for reversing chemotherapy resistance.

The invention discloses a Weissella sinus strain as well as a fermentation product filtrate and a biological product thereof, and belongs to the technical field of cosmetics. The strain can be used in the field of cosmetics, has excellent HAS inhibition capability, also has remarkable DPPH and ABTS free radical scavenging capability, and can realize a good antioxidant effect; secondly, under various concentrations, fermentation product filtrate can remarkably reduce the proportion of SA-beta-Gal positive cells, gene expression of various matrix metalloproteinases can be remarkably inhibited, and a certain effect of reducing cell senescence markers is achieved; in addition, the fermentation product filtrate can inhibit the activity of tyrosinase in vitro, can also significantly inhibit the generation of melanin in a zebra fish model, and has the potential of being used as a tyrosinase inhibitor or a melanin generation inhibitor; the fermentation product filtrate can also significantly inhibit the secretion amount of a cell inflammatory factor NO, has a good soothing effect, and has a certain ability to regulate the skin micro-ecology.

The invention discloses a flora-friendly selective antifungal peptide HRI and application thereof, and belongs to the technical field of novel antibacterial materials. The antifungal peptide HRI provided by the invention can only selectively resist pathogenic fungi instead of bacteria and especially does not resist symbiotic bacteria on the premise of maintaining flora balance, has relatively high biological safety, and has a certain inhibition effect on matrix metalloproteinase (MMP-9).

This invention provides a highly stable recombinant type XVII collagen, its construction method, and its applications, belonging to the field of bioengineering technology. The invention selects the amino acid sequence of natural human type XVII collagen as the basic unit and repeatedly replicates it to obtain recombinant type XVII collagen. The design process of the recombinant type XVII collagen avoids unstable GXY triplets, eliminates potential matrix metalloproteinase cleavage sites and glycosylation sites, and retains the KGD active sequence, thus reducing the probability of containing easily degraded sites. The sequence fragment of the recombinant type XVII collagen is derived from the full-length sequence of the natural collagen gene, exhibiting excellent solubility, bioactivity, and high stability. It remains stable under high-temperature storage conditions and without alkaline conditions, making it suitable as a raw material for the production of pharmaceuticals, medical devices, biomaterials, or cosmetics, demonstrating significant practicality.

The application relates to the technical field of genetic engineering, in particular to a sucrose phosphorylase mutant and application thereof in synthesis of alpha-maronia. Streptococcus parasanguinis The application is characterized in that the histidine at the 152th position of the wild-type sucrose phosphorylase from Streptococcus sanguis is mutated into threonine, and the isoleucine at the 336th position is mutated into proline, so that the sucrose phosphorylase mutant is obtained, the catalytic activity and stability of the sucrose phosphorylase are significantly improved. When sucrose and hydroquinone are used as substrates, the yield of alpha-maronia is increased by more than 40% compared with the wild type, and the catalytic reaction time can be greatly shortened.

The application discloses oleanane triterpene saponin compounds with improved mitochondrial energy anti-aging, a preparation method and application thereof, and belongs to the technical field of medicines and cosmetics. Through systematic chemical component research on Zhejiang Hongshan tea flowers, two new oleanane triterpene saponin compounds CK and CL are separated, and the chemical structures are determined by using high-resolution mass spectrometry and nuclear magnetic technology. In-vitro anti-photoaging activity research shows that the new compounds CK and CL provided in the application have good protection effects on ultraviolet-induced fibroblast photoaging, can significantly improve the content of type I collagen, reduce the expression of matrix metalloproteinases mmp1 and mmp3 , increase the generation of mitochondrial autophagosomes and lysosomes, promote mitochondrial autophagy, relieve mitochondrial damage and improve cell senescence. The preparation method provided in the application is simple, and the activity is significant, so that the application is expected to be developed into a new anti-skin aging medicine or cosmetic.

This invention provides the application of costunolide in the preparation of a drug for preventing posterior capsule opacification. Costunolide effectively reduces posterior capsule opacification after extracapsular lens extraction (ECLE) and exhibits significant anti-inflammatory and anti-fibrotic effects in both in vitro and in vivo models. Mechanistic studies have identified matrix metalloproteinase 8 (MMP8) as a key downstream effector of costunolide, confirming that costunolide inhibits MMP8 expression, thereby blocking the transformation of lens epithelial cells (LECs) into mesenchymal cells and subsequent fibrotic processes. This lays a solid foundation for developing targeted therapies for posterior cataract, a common surgical complication.

Disclosed is an in vitro method for assessing whether a human subject has periodontitis. The method comprises detecting, in a sample of saliva from said subject, the concentrations of the proteins Hepatocyte Growth Factor (HGF) and Matrix Metalloproteinase 8 (MMP-8). Based on the concentrations determined, and adding age, and possibly other demographic markers such as sex and / or BMI, a testing value reflecting the joint concentrations is determined for said proteins, in combination with one or more demographic markers. The testing value is compared with a threshold value. The threshold reflects in the same manner the joint concentrations and the age, and possibly other demographic markers, as associated with periodontitis and may be seen as an upper limit of testing values as seen in a population of subjects without periodontitis. Thereby a testing value at or above the threshold value is indicative for periodontitis in said subject.

The invention discloses a functionalized acellular matrix material and a preparation method thereof, and relates to the technical field of biomedical treatment, the functionalized acellular matrix material comprises: a composite ECM skeleton, which is prepared by compounding squid sheaths and amniotic membranes and performing acellular treatment; the multi-stage response degradation switch comprises a matrix metalloproteinase sensitive peptide cross-linking bridge and a polythioether-polylactic acid block copolymer oxidation response chain segment; the natural biological conductive network is formed by compounding an in-situ polymerization product of a mussel byssus protein conductive fragment and amino-modified graphene quantum dots, the characteristics of squid sheaths and amniotic membranes are fused to construct a composite ECM skeleton, a multi-stage response degradation switch is integrated, and the comprehensive performance of the material is optimized; meanwhile, a natural biological conductive network is introduced, so that the electroactivity is improved, and a safe, efficient and powerful novel stent solution is provided for tissue engineering.

This invention relates to a ZIF-8-based composite nanoparticle with a core-shell structure. The core is a zeolite imidazole ester backbone ZIF-8 carrier, and the pores of the ZIF-8 core are loaded with a photothermal agent. Liposomes are coated on the outer surface of the core as a shell, and CD90 antibodies are coupled to the surface of the liposomes. The composite nanoparticle targets mesenchymal stem cells, thereby more effectively delivering zinc ions into mesenchymal stem cells (MSCs) to regulate MMP-10 (matrix metalloproteinase-10) expression. The composite nanoparticle can be used to prepare drugs or medical dressings for treating bone defects and / or promoting vascularized bone regeneration.

The invention relates to a recombinant protein, printing ink, a 4D scaffold and a preparation method and application thereof, and belongs to the technical field of biology. The recombinant protein provided by the invention can provide extracellular matrix-like structure support, catalyzes generation of dopamine groups, endows the recombinant protein with bionic adhesion performance, and meanwhile can regulate and control the activity of matrix metalloproteinase, maintain balance of scaffold degradation and tissue regeneration, target inflammatory factor genes and relieve local inflammatory response. The recombinant protein, the P (NIPAM-co-AA) copolymer and the KLT peptide-loaded mesoporous SiO2 jointly form the printing ink, and the printing ink can be used for printing a 4D biological scaffold, not only has the effect of the recombinant protein, but also has the effects of temperature responsiveness and promoting cell proliferation and vascularization. Meanwhile, due to the fact that a TPMS structure model is adopted in the 4D stent, directional curling can be achieved, and the better mechanical property is achieved; the hydrogel can be used for tissue repair and filling, tissue regeneration is promoted, and wounds are rapidly healed.

The invention relates to application of a Piezo1 inhibitor in preparation of a medicine for treating keratoconus, and belongs to the technical field of preparation and application of biological medicines. By inhibiting a Piezo1 signal channel, overexpression of matrix metalloproteinase (MMPs) and release of inflammatory factors are reduced, so that thinning of corneal basis and disease progression are delayed or prevented. Gene silencing, pharmacological intervention, animal model construction and multi-dimensional detection verification prove that the GsMTx4 eye drops have good safety, effectiveness and conversion application prospects, and a new strategy and an experimental basis are provided for medicine treatment of cornea conus.

The application discloses application of extracellular vesicles from Eclipta prostrata L. The extracellular vesicles are extracted from Eclipta prostrata L. by using ultracentrifugation and ultrafiltration, and the extracted vesicles are complete in appearance and good in dispersibility, and have the characteristics of high yield, fast separation, low cost and easy scaling. The extracted vesicles can be successfully taken by animal cells. After being taken, the vesicles play the roles of antioxidation and anti-aging, can significantly reduce ultraviolet-induced matrix metalloproteinase 1 (MMP1) expression, promote collagen I (COL-I) generation, improve ultraviolet-induced skin photoaging, and the effect is stronger than that of Eclipta prostrata L. alcohol extract, so that the extracellular vesicles from Eclipta prostrata L. provide a new strategy for skin aging and anti-aging treatment.

This invention discloses a targeted nanoparticle for calcium overload therapy combined with photothermal therapy, specifically involving a lipid-modified cRGD-targeting, MMP-responsive, and pH-sensitive calcium carbonate nanoparticle loaded with indocyanine green (ICG). This invention uses pH-sensitive calcium carbonate, which can decompose and exfoliate within lysosomes, as the matrix material. It leverages cRGD's specific targeting of tumor cells, the tumor microenvironment-specific high expression of matrix metalloproteinases (MMPs) to induce the release of DPPA-1 within the tumor microenvironment, and the low pH characteristic within lysosomes to achieve a combined anti-tumor effect of phototherapy and immunotherapy.

The invention belongs to the technical field of biomedical engineering and cell therapy, and particularly relates to a preparation method of a mesenchymal stem cell exosome capable of improving an anti-inflammatory function. The core is a collaborative design of composite biochemical pre-stimulation and inflammatory microenvironment response type three-function targeting anchoring. A tumor necrosis factor-alpha with a concentration of 5-8 ng / mL, a resveratrol derivative with a concentration of 2-5 [mu] mol / L and glutathione with a concentration of 10-20 [mu] mol / L are adopted for reverse synergistic pre-stimulation, such that an anti-inflammatory pathway is activated; a vascular cell adhesion molecule-1 targeting domain-matrix metalloproteinase-9 sensitive connecting arm-LL-37 anti-inflammatory domain fusion polypeptide is anchored, so that precise targeting and response release are realized. According to the method, the problems of insufficient anti-inflammatory activity, poor targeting and off-target of the exosome are solved, the enrichment amount of an inflammatory site is increased by 2.5-4 times, the TNF-alpha inhibition rate reaches 90%-95%, and the exosome is suitable for treating inflammatory diseases.

This invention discloses *Wesleyanus esculenta* strain, its fermentation product filtrate, and its biological products, belonging to the field of cosmetic technology. This strain can be used in cosmetics, exhibiting excellent HAS inhibition ability and significant DPPH and ABTS free radical scavenging capabilities, achieving good antioxidant effects. Secondly, at various concentrations, its fermentation product filtrate can significantly downregulate the proportion of SA-β-Gal positive cells and significantly inhibit the gene expression of various matrix metalloproteinases, demonstrating a certain effect in reducing cellular aging markers. Furthermore, its fermentation product filtrate can inhibit tyrosinase activity in vitro and significantly inhibit melanin production in a zebrafish model, showing potential as a tyrosinase inhibitor or melanin production inhibitor. Its fermentation product filtrate can also significantly inhibit the secretion of the cellular inflammatory factor NO, exhibiting good soothing effects and a certain ability to regulate the skin microecology.

This invention provides the use of Cm-CATH2 in the preparation of drugs for treating silicosis, belonging to the field of biomedical technology. This invention provides the application of Cm-CATH2 and / or pharmaceutically acceptable salts of Cm-CATH2 in the preparation of drugs for treating silicosis, and verifies the therapeutic effect of Cm-CATH2 on silicosis animal models by constructing such models. The results show that Cm-CATH2 can act on silicosis at multiple targets after the early stage of silicosis in animal models. It reduces oxidative stress levels by downregulating lactate dehydrogenase (LDH), downregulates matrix metalloproteinase 2 (MMP2) and extracellular matrix glycosaminoglycans (GAG), and ultimately reduces collagen III (COL-III) levels, thereby achieving an anti-fibrotic effect. This multi-target approach can effectively alleviate fibrosis progression. Therefore, Cm-CATH2 can be used to treat silicosis, and a dose-response effect exists, with good efficacy at high doses.

The present invention is directed to a cellular therapeutic composition for treating diabetes in a subject comprising a therapeutically effective amount of insulin producing cells; and a therapeutically effective amount of modified mesenchymal stem cells, wherein the mesenchymal stem cells have been modified to increase expression of matrix metalloproteinase-9 (MMP-9) or a fragment or variant thereof.

This invention belongs to the field of nanoparticle hydrogel scaffold technology, providing an MMP-responsive nanoparticle hydrogel scaffold and its application in the treatment of fibrous bone dysplasia. The nanoparticle hydrogel scaffold is prepared by cross-linking and curing triglyceride monostearate nanoparticles, 3-aminophenylboronic acid-modified hyaluronic acid, and dopamine-modified hyaluronic acid. This invention is based on the first discovery that the concentration of matrix metalloproteinases (MMPs) around fibrous bone dysplasia lesions is a biomarker reflecting the "activity and treatment response of fibrous bone dysplasia lesions," and based on this discovery, provides an MMP-responsive nanoparticle hydrogel scaffold and its application in the treatment of fibrous bone dysplasia. This nanoparticle hydrogel scaffold can achieve perilesional drug delivery and sustained MMP-responsive drug release through injection, thereby providing a local treatment strategy for fibrous bone dysplasia.

The invention discloses an application and a method of hydrogel in vascularization culture of organoids, in the application, the hydrogel is prepared from a precursor composition, the precursor composition is an aqueous solution, and the precursor composition comprises, by weight, 10-20% of an aqueous solution, and 10-20% of an aqueous solution. W / v: the concentration of the norbornene modified heparin is 0.2-2%, the concentration of the norbornene modified gelatin is 0.5-5%, the concentration of the sulfydryl four-arm polyethylene glycol is 0.3-3%, the concentration of the photoinitiator is 0.01-0.1%, the concentration of the matrix metal protein peptidomimetic MMP is 0.05-0.5%, the sequence of the matrix metal protein peptidomimetic MMP is shown as SEQ ID NO.3, the norbornene modified heparin is obtained by modifying a heparin raw material, and the thickness of the matrix metal protein peptidomimetic MMP is 0.5-1 mm. The norbornene modified gelatin is obtained by modifying a gelatin raw material. According to the invention, the vascularization culture of the tumor-like organs is realized, and the large-scale vascularization culture of the tumor-like organs is facilitated.

This invention discloses a logic-responsive biomolecule carrier based on a phase separation system, its construction method, and its applications. The carrier is based on the attraction between cationic peptides with different logic responses and negatively charged biomolecules such as DNA or RNA, driving liquid-liquid phase separation and forming droplet-like particle structures. The carrier of this invention can selectively use protein kinase A (PKA) to phosphorylate peptides and use matrix metalloproteinases (MMPs) or glutathione (GSH) to cleave the peptide chain, thereby changing the charge density of the peptide to control the controlled release of biomolecules. It exhibits excellent biocompatibility, resistance to enzymatic degradation, and transfection efficiency, enabling effective delivery of biomolecules.